Transfer and functional consequences of dietary microRNAs in vertebrates: concepts in search of corroboration: negative results challenge the hypothesis that dietary xenomiRs cross the gut and regulate genes in ingesting vertebrates, but important questions persist.

Witwer KW, Hirschi KD - Bioessays (2014)

Bottom Line:
RNA interference (RNAi) mechanisms of Caenorhabditis elegans are enhanced by uptake of environmental RNA and amplification and systemic distribution of RNAi effectors.In this article, we review the evidence for and against a significant role for dietary miRNAs in influencing gene expression, and make recommendations for future studies.Also watch the Video Abstract.

fig04: Non-canonical (RISC-independent) actions of small RNA. A: TAR-derived RNA in HIV-1 transcriptional control. Effects on transcription have been reported for miRNA and other small RNA. Cleavage of a 5′ structured element (TAR, 1) in the nascent HIV-1 transcript may interact with the corresponding sequence in the integrated DNA (2) and lead to further degradation of the transcript (3), enforcing HIV latency. B: Small RNA may influence secondary/tertiary structure by binding complementary elements separated by considerable distance in the primary sequence.

Mentions:
Nor is canonical RISC-mediated suppression the only conceivable or known mechanism of small RNA function. Nuclear effects of small RNA (Fig. 4A) have been reported [119], including the interference of a TAR-derived RNA with retroviral transcription [120,121]. Since only one genomic integration of HIV-1 typically occurs per cell, chromatin-mediated suppressive mechanisms might require fewer copies of suppressive small RNAs than would be needed to silence many transcripts. Indeed, this mechanism would involve, at most, one small RNA per transcriptional event (Fig. 4A). Althaus et al. [122] also reported host and viral small RNAs interactions with the HIV-1 transcript that did not necessarily involve RISC. Interestingly, the reported resistance of HIV-1 to RISC-mediated miRNA regulation [116] could theoretically be due in part to effects of small RNA, which may enforce transcript structure and transport [123,124]. Structural contributions of small RNA could of course be extended to any type of RNA molecule in the cell (Fig. 4B).

Transfer and functional consequences of dietary microRNAs in vertebrates: concepts in search of corroboration: negative results challenge the hypothesis that dietary xenomiRs cross the gut and regulate genes in ingesting vertebrates, but important questions persist.

fig04: Non-canonical (RISC-independent) actions of small RNA. A: TAR-derived RNA in HIV-1 transcriptional control. Effects on transcription have been reported for miRNA and other small RNA. Cleavage of a 5′ structured element (TAR, 1) in the nascent HIV-1 transcript may interact with the corresponding sequence in the integrated DNA (2) and lead to further degradation of the transcript (3), enforcing HIV latency. B: Small RNA may influence secondary/tertiary structure by binding complementary elements separated by considerable distance in the primary sequence.

Mentions:
Nor is canonical RISC-mediated suppression the only conceivable or known mechanism of small RNA function. Nuclear effects of small RNA (Fig. 4A) have been reported [119], including the interference of a TAR-derived RNA with retroviral transcription [120,121]. Since only one genomic integration of HIV-1 typically occurs per cell, chromatin-mediated suppressive mechanisms might require fewer copies of suppressive small RNAs than would be needed to silence many transcripts. Indeed, this mechanism would involve, at most, one small RNA per transcriptional event (Fig. 4A). Althaus et al. [122] also reported host and viral small RNAs interactions with the HIV-1 transcript that did not necessarily involve RISC. Interestingly, the reported resistance of HIV-1 to RISC-mediated miRNA regulation [116] could theoretically be due in part to effects of small RNA, which may enforce transcript structure and transport [123,124]. Structural contributions of small RNA could of course be extended to any type of RNA molecule in the cell (Fig. 4B).

Bottom Line:
RNA interference (RNAi) mechanisms of Caenorhabditis elegans are enhanced by uptake of environmental RNA and amplification and systemic distribution of RNAi effectors.In this article, we review the evidence for and against a significant role for dietary miRNAs in influencing gene expression, and make recommendations for future studies.Also watch the Video Abstract.